In many applications of microfluidic systems, it is necessary to control a very large number of microfluidic channels in order to control various analysis or synthesis steps in a system or in a process.
German patent application DE 10 2007 032 951 A1 describes a microfluidic system that uses a mediating medium. Such structures, referred to as indirect microfluidic systems, are suitable for applications in critical analytical applications, for example, in biomedical technology, thanks to the fact that they are disposable and that expensive microfluidic components can be operated contamination-free. However, such systems require a large number of 2/2-way valves, that is to say, valves that block or free a microfluidic channel. The number of channels to be controlled here can easily range from a few dozen to more than a hundred.
Such systems cannot be operated reliably by either small implemented conventional valves or by directly controlled micro-valves, since the control technology becomes very complex with such a large number of valves. Moreover, the structural size of such systems also quickly increases disproportionately,
U.S. Pat. No. 6,575,188 B2, European patent application 0 368 306 B1 and European patent application 0 731 303 B1 describe individual thermal valve cells that each have a heat source and a heat sink. The opening and closing of a microfluidic channel is carried out by selectively switching on and off the heat source or the heat sink. For purposes of switching off, the microfluidic channel is closed in a defined area by local freezing, and for purposes of switching on, it is opened again by local heating and the resultant melting of the icing.
These systems call for a 1-to-1 control, that is to say, the valves are each opened and closed again individually, so that each valve can be associated with its own control line. The advantage in comparison to systems that are based on moving mechanical components such as membranes or piezo actuators is that the thermal valves work passively, as a result of which they are much more sturdy, less error-prone and thus more stable during operation. Particularly in terms of manufacturing tolerances and fits, thermal valves are superior to the valves used in conventional valve technology. The creation of the blocking volume intrinsically has a precise fit, so that no valve leaks are possible due to inaccurately fitting shapes, which is a major problem especially in conventionally designed, miniaturized microfluidic valves. In particular, a valve is configured in such a way that the heat source and the heat sink are uncoupled from the microfluidic channel. The microfluidic channel is then independently closed off and configured on a separate component, the heat source and the heat sink can be used again when the microfluidic channel is disposed of, for example, because it is contaminated or clogged. Furthermore, these valves are also less expensive to manufacture, since they do not contain any actual valve components. Rather, the valve function is achieved by substances already present in the system, namely, the content of the microfluidic channel. Another advantage of these systems is that they are independent of the selected material of the microfluidic channel. The material can be adapted to the required application in each case and can be made, for example, of plastic, ceramic or silicon. Regardless of the selection of the material, the described thermal valve technology can be transferred to all materials since the valve uses only the content of the channel for the valve function.
In the described state, thermal valves can be used in order to open or to close channels in certain places in microfluidic systems. However, if the number of channels to be controlled is very large (in the range from hundreds to thousands), then thermal valves would be as unsuitable as any other valve that is configured for 1-to-1 control. The control resources needed for such a system are simply too great.
U.S. Pat. No. 7,143,785 B2 describes a fluidic multiplexer on the basis of membrane valves that is actuated by compressed air. Furthermore, U.S. Pat. No. 3,599,525 A, U.S. Pat. No. 5,775,371 A and U.S. Pat. No. 6,202,687 B1 describe systems that can carry out highly complex control tasks by means of compressed-air control. A drawback here is that even though the concept of multiplexing allows a reduction of the control lines, at the same time, it intrinsically increases the number of actually present valves. For example, a 3-bit fluidic multiplexer results in a number of 8 controllable microfluidic channels. However, these channels each have three intersections with the control lines at which the channel is to be configured so that it can be switched. Each of these intersections is thus effectively a single valve. Thus, for a 3-bit fluidic multiplexer, this results in a total sum of 3×8=24 individual valves. If these valves are configured as conventional micro-mechanical valves, then the number of requisite valves is tripled in comparison to a 1-to-1 control. With a higher number of control lines, this value is multiplied by an even greater factor. Another drawback of the compressed-air control is that the actual valve is not made up only of the micro-technically configured valve component. The pressure exerted on the fluidic valves, in turn, has to be controlled by a pneumatic valve, as a result of which the number of actually present valves is further increased, especially since the two valve types, that is to say, fluidic valves in the microfluidic component and pneumatic valves outside of the fluidic component, are of a different design. Furthermore, only very few materials can be used to make the described micro-technical valves. They require a very soft material, especially a soft polymer, e.g. polydimethylsiloxane (PDMS). If the application calls for another material, for instance, metal or ceramic, then the valve function cannot be achieved in this manner.
Therefore, a fluidic multiplexer in classic valve technology increases the error-proneness of the system, since for every single valve, a certain probability exists that it will come out of the production process with a defect. For the fluidic multiplexer described in U.S. Pat. No. 7,143,785 B2, a total sum of over 2000 individual micro-mechanical valves is needed, that is to say, even at a reject rate of just 0.1%, this would already amount to two valves in this system. Here, it should be kept in mind that already just one defective valve will put the entire multiplexer out of operation. The reduction of the complexity of the actuation is only achieved at the expense of the reliability of the system.
Moreover, all of the described fluidic multiplexers described have a problem: the structure of the valves and of the actuator system is intrinsically linked to the microfluidic structure. If the microfluidic channel structure is to be disposed of, for example, because the structure is contaminated or clogged, the entire actuator system also has to be disposed of, since it is permanently joined to the microfluidic structure. This condition further reduces the reliability of these systems and makes them unsuitable particularly for applications that call for a frequent replacement of the channel structure, especially biomedical applications, which require that all of the system components that have ever come into contact with an analyte have to be replaced after each measurement.